Dimethylacetamide → [(1-{2-Fluoro-4-[6-({[3-(trifluoromethyl)phenyl]acetyl}amino)pyridin-3-yl]phenyl}cyclobutyl)oxy]acetic acid

HRID 885138ノート

反応式

HRID 885138 の反応式
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH2:9][C:10]([NH:12][C:13]2[N:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=2)=[O:11])[CH:6]=[CH:7][CH:8]=1.Br[C:25]1[CH:30]=[CH:29][C:28]([C:31]2([O:35][CH2:36][C:37]([OH:39])=[O:38])[CH2:34][CH2:33][CH2:32]2)=[C:27]([F:40])[CH:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)C(=O)C>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].O.C(O)C>[F:40][C:27]1[CH:26]=[C:25]([C:16]2[CH:17]=[N:18][C:13]([NH:12][C:10](=[O:11])[CH2:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:23])([F:22])[F:1])[CH:4]=3)=[CH:14][CH:15]=2)[CH:30]=[CH:29][C:28]=1[C:31]1([O:35][CH2:36][C:37]([OH:39])=[O:38])[CH2:34][CH2:33][CH2:32]1

参加物

8

反応物 4

HCID 31374DimethylacetamideHCID 62657Potassium Phosphate, TribasicHCID 687205752-(1-(4-Bromo-2-fluorophenyl)cyclobutoxy)acetic acidHCID 687207776-({[3-(Trifluoromethyl)phenyl]acetyl}amino)pyridin-3-ylboronic acid

生成物 1

HCID 25106327[(1-{2-Fluoro-4-[6-({[3-(trifluoromethyl)phenyl]acetyl}amino)pyridin-3-yl]phenyl}cyclobutyl)oxy]acetic acid

試薬・触媒・溶媒 3

HCID 178454861HCID 178454861、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
90 °C

実験手順

A 4 mL vial was charged with the product from Example 61A (17.7 mg, 0.055 mmol) and the product from Example 60B (16.56 mg, 0.055 mmol), dibasic potassium phosphate (28.5 mg, 0.164 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium (II) dichloride (0.357 mg, 0.546 μmol), N,N-dimethylacetamide (1 ml), ethanol (1.000 mL), and water (0.500 mL). The suspension was stirred and heated to 90° C., whereupon the reaction became homogenous. After heating at 90° C. for 1 hour, the reaction was cooled to room temperature. The reaction was then partitioned between with ethyl acetate (2 mL) and water (2 mL). The layers were separated, and the organic was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase HPLC (mobile phase: 10%-100% acetonitrile in 0.1% trifluoroacetic acid aqueous solution during 60 min, G18 column) to give the title product. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.59-1.72 (m, 1H), 1.95-2.07 (m, 1H), 2.38-2.45 (m, 4H), 3.65 (s, 2H), 3.89 (s, 2H), 7.46-7.52 (m, 1H), 7.55-7.67 (m, 5H), 7.73 (s, 1H), 8.11-8.18 (m, 2H), 8.73 (br s, 1H), 10.94 (s, 1H). MS (ESI) m/z 503 [M+H]+.

後処理

  1. temperatureAfter heating at 90° C. for 1 hour
  2. temperaturethe reaction was cooled to room temperature
  3. customThe reaction was then partitioned between with ethyl acetate (2 mL) and water (2 mL)
  4. customThe layers were separated
  5. dry with materialthe organic was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by reverse-phase HPLC (mobile phase: 10%-100% acetonitrile in 0.1% trifluoroacetic acid aqueous solution during 60 min, G18 column)

出典と根拠

ORDレコード
ord-7deb189bf755417fbb60bf976c54352a
出典データセット
uspto-grants-2012_08
特許番号
US08242139B2

反応ノート

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